1. Field of the Invention
This invention relates to a process for producing .alpha.-L-aspartyl-L-phenylalanine methyl ester (hereinafter referred to as .alpha.-APM) and for recovering L-phenylalanine from the side stream generated from processes which produce .alpha.-APM.
2. Discussion of the Background
.alpha.-APM is about 200 times as sweet as sucrose and is in great demand as a dietary sweetener due to its good sweet taste and low calorie content. Various processes for producing .alpha.-APM are known, for example a process which comprises reacting N-protected L-aspartic anhydride with L-phenylalanine methyl ester (U.S. Pat. No. 3,786,039), a process which comprises reacting N-protected L-aspartic anhydride with L-phenylalanine (U.S. Pat. No. 4,173,562), and a process which comprises condensing N-benzyloxycarbonyl-L-aspartic acid and L-phenylalanine methyl ester with an enzyme (Japanese Patent Application Laid-open No. 92729-1978). However, to employ them for low cost industrial process, it is necessary to recover and reuse L-phenylalanine and L-aspartic acid from side streams obtained during the .alpha.-APM production process such as .alpha.-APM mother liquor or .alpha.-APM. HCl mother liquor, since these side streams contain a significant amount of L-phenylalanine derivatives, L-aspartic acid derivatives and .beta.-L-aspartyl-L-phenylalanine methyl ester and .alpha.-APM. Of these, it is very important to efficiently recover L-phenylalanine, which is an expensive amino acid. Known processes for recovering L-phenylalanine from a side stream generated during a process for production of .alpha.-APM include a process disclosed in Japanese Patent Application Laid-open No. 97812-1973. The process comprises hydrolysis of a solution containing .beta.-L-aspartyl-Lphenylalanine methyl ester in the presence of a mineral acid, adjusting the reaction solution to pH 6 for crystallization and separation of L-phenylalanine. However, the mother liquor after separation still contains a considerable amount of L-phenylalanine. Accordingly, the recovery may be further improved if the solubility of L-phenylalanine can be reduced.
The problem solved by the invention is that of establishing an industrial process to efficiently recover L-phenylalanine from side streams generated from the production of .alpha.-APM. The present inventors have intensively studied a process for efficient recovery of L-phenylalanine from side streams obtained during production of .alpha.-APM. As a result, we have found unexpectedly that the solubility of L-phenylalanine in aqueous solutions is reduced, and recovery of L-phenylalanine is improved if L-aspartic acid or an aqueous solution thereof is present when the pH of a reaction mixture obtained by hydrolysis of said side stream with a mineral acid is adjusted to 5-6, thus precipitating L-phenylalanine.